This grant application is in response to RFA AI-05-019 "Cooperative Research Partnerships for Biodefense". It is a product of the long-standing partnership of the University of Virginia and TechLab, Inc in applied research on amebiasis. Together we propose to develop and test in mice an acellular vaccine for the prevention of amebic colitis due to infection with Entamoeba histolytica, an NIAID Category B priority pathogen. The vaccine will be composed from the 3 subunits that comprise the E. histolytica Gal/GalNAc lectin. Focus on the Gal/GalNAc lectin is for three major reasons: the Gal/GalNAc lectin mediates parasite adherence and cytotoxicity, human immunity is associated with mucosal IgA anti-Gal/GalNAc lectin, and vaccination with the Gal/GalNAc lectin protects from amebic colitis in an animal model. Parallel and highly interactive projects will: (1) empirically test acellular vaccines comprised of each of the 3 lectin subunits alone and in combination;(2) systematically investigate mechanisms of acquired immunity in the mouse;and (3) adapt the prototype vaccine from Aim 2 for the use of adjuvants that optimally promote the mechanisms of protective immunity identified in Aim 2 and which are acceptable for human use. Support is requested for the early stages of product development, up to but not including phase I trails. Successful completion of these studies will result in a Gal/GalNAc lectin-based vaccine for amebiasis that is ready for GMP production and phase I studies.